Monoclonal antibodies (mAbs) are attractive vehicles for targeting radiation to tumors because of their ability to react specifically with molecular determinants on cancer cells. However, the anticipated impact of labeled mAbs on the clinical management of cancer has yet to be achieved; loss of label from the mAb in vivo and uptake of radioactivity in normal tissues have impeded their clinical application. Iodine-131 is the most frequently used nuclide in clinical radioimmunotherapy, but its usefulness has been compromised by in vivo dehalogenation of mAbs labeled via conventional procedures.
Radiolabeled mAbs could play an important role in the diagnosis and treatment of cancer if the molecular specificity inherent in the mAb-antigen interaction can be successfully exploited to selectively deliver radionuclides to tumors. For many types of cancer, radioimmunotherapy is an attractive alternative to external beam radiation therapy and systemically administered chemotherapy, treatments that are frequently ineffective because of dose-limiting toxicities to normal tissues. Radioimmunoscintigraphy is appealing not only for lesion detection but also as a means for determining which patients are suitable candidates for labeled mAb therapy. Numerous clinical studies have confirmed the ability of labeled mAbs to localize in both primary and metastatic cancers (reviewed in Britton and Granowska, 1996; Larson, 1995), and in patients with radiosensitive tumors, significant therapeutic responses have been obtained with 131I-labeled mAbs (Press et al., 1995; Kaminski et al., 1996). However, other tumors have proven to be less radiosensitive, presumably due to the low level of radionuclide retained in tumor and the significant accumulation of radioactivity in normal organs (Kairemo, 1996; Bast et al., 1997). There remains a need in the art for improved techniques and reagents to selectively target both therapeutic and diagnostic radiolabels to tumor cells.